Automatic analyzer

ABSTRACT

To be adapted to various types of latex reagents for detecting scattered light and thereby measuring agglutination reactions with high sensitivity while sufficiently ensuring integration time. To be adapted to various types of latex particles of different particle sizes, a plurality of light receivers are arranged in a plane perpendicular to the direction of cell movement by rotation of a cell disk. To ensure sufficient integration time, the angle between the optical axis of the irradiation light and each of a plurality of optical axes of scattered light viewed from above the cell is made equal to or less than 17.7° including a mounting error.

CROSS REFERENCE TO RELATED APPLICATION

This application is continuation of U.S. patent application Ser. No.14/484,384, filed on Sep. 12, 2014, which is a continuation of U.S.patent application Ser. No. 13/382,316, filed on Feb. 1, 2012, which isnow U.S. Pat. No. 8,852,511, which is a U.S. National Stage PatentApplication under 35 U.S.C. §371 of International Patent Application No.PCT/JP2010/061369, filed on Jul. 5, 2010 the entire contents of each ofwhich are hereby incorporated by reference.

TECHNICAL FIELD

The present invention relates to a sample analyzer that analyzes asample to determine the amount of constituent contained therein, and forexample, an automatic analyzer that analyzes blood or urine to determinethe amount of constituent contained therein.

BACKGROUND ART

As a sample analyzer for analyzing a sample to determine the amount ofconstituent contained therein, there has been widely used an automaticanalyzer that emits light from a light source to a sample or a reactionmixture of a sample and a reagent; measures the amount of transmittedlight of a single or a plurality of wavelengths obtained therefrom tocalculate the absorbance; and determines the amount of constituent fromthe relation between the absorbance and the concentration according tothe Beer-Lambert law (for example, see Patent Literature 1). Theanalyzer has a cell disk that repeats rotation and termination and alarge number of cells holding a reaction mixture are arrangedcircumferentially thereon. During the cell disk rotation, a presettransmitted light measuring unit measures the change in absorbance overtime for about ten minutes at a specific time interval.

The automatic analyzer includes a system for measuring the amount oftransmitted light. The reaction of a reaction mixture is roughly dividedinto two types: an enzyme-substrate color reaction and anantigen-antibody agglutination reaction. The former is a biochemicalanalysis and includes LDH (lactate dehydrogenase), ALP (alkalinephosphatase), AST (aspartate aminotransferase), and the like as the testitems. The latter is an immunoassay and includes CRP (C-reactiveprotein), IgG (immunoglobulin), RF (rheumatoid factor), and the like asthe test items. The analyte to be measured by the latter immunoassay hasa low blood level, and hence high sensitivity is required.Conventionally, high sensitivity has been provided by an immunologicallatex agglutination in such a manner that a reagent with an antibodysensitized (bound) to a latex particle surface is used; when aconstituent contained in a sample is recognized and agglutinated, lightis emitted to a reaction mixture; and then the mount of constituentcontained in the sample is quantified by measuring the amount of lighttransmitted but not scattered by the latex aggregate.

Further, as the analyzer, an attempt has been made to increasesensitivity not by measuring the amount of transmitted light but bymeasuring the amount of scattered light. For example, there aredisclosed a system that uses a diaphragm to separate the transmittedlight and the scattered light and measure the absorbance and thescattered light at the same time (Patent Literature 2); a configurationin which precision is increased on a high concentration side bymeasuring the scattered light reflected by a large aggregate formed as aresult of advanced agglutination reaction (Patent Literature 3); amethod in which in front of and at the back of a reactor vessel, anintegrating sphere is used to measure an average amount of light of eachof the forward scattered light and the backward scattered light andcorrect turbidity changes due to cell dislocation (Patent Literature 4);a method of facilitating reduction in size and adjustment of theanalyzer by arranging a fluorescent light—scattered light measurementdetection system on the same plane as the direction of cell rotation(Patent Literature 5), and the like.

CITATION LIST Patent Literature

-   Patent Literature 1: U.S. Pat. No. 4,451,433-   Patent Literature 2: JP 2001-141654 A-   Patent Literature 3: JP 2008-8794 A-   Patent Literature 4: JP 10-332582 A-   Patent Literature 5: JP 1-295134 A

SUMMARY OF INVENTION Technical Problem

The amount of scattered light greatly changes according to thewavelength of irradiation light, the particle size of a particle as thescatterer, and the scattering angle. Accordingly, in order to obtainhigh sensitivity, it is important to detect the scattered light usingthe scattered light receiving angle according to the particle size of alatex reagent. Various types of latex reagents are used in an automaticanalyzer as a general-purpose apparatus. The particle size of the latexparticle is generally about 0.1 μm to 1.0 μm, but the particle size isnot disclosed. According to conventional techniques, even an automaticanalyzer configured to detect scattered light cannot handle latexreagents of various particle sizes. Thus, the arrangement capable ofdetecting a latex reagent of any particle size with high sensitivity isnot clarified.

Further, in recent years, in order to reduce reagent running costs,reduction in cell size is progressing by reducing the amount of reactionmixture, resulting in the reduction in cell size with an optical pathlength of about 5 mm and a cell width of about 2.5 mm. Particularly, thecell width is shrinking. However, the measurement of the change inabsorbance over time requires data in a shorter time interval, and hencethe cell rotation speed cannot be reduced. Therefore, the integrationtime for each measurement is shortened. When the automatic analyzermeasures the scattered light, the automatic analyzer needs to measurethe rotating cells. Particularly the amount of scattered light issmaller than that of transmitted light, and hence it is important tosecure the integration time.

Patent Literature 2 discloses a configuration capable of measuring thescattered light and the transmitted light at the same time, but does notreveal the configuration of arranging a scattered light receiveraccording to various types of latex particle sizes. Patent Literature 2uses a diaphragm to obtain the scattered light around the entirecircumference, but does not consider the cell width or the integrationtime.

Patent Literature 3 obtains the scattered light for the purpose ofincreasing the precision on the high concentration side, but is noteffective for increasing sensitivity on the low concentration side.

Patent Literature 4 uses an integrating sphere to average the scatteredlight, but is not effective for increasing sensitivity. In addition,Patent Literature 4 is a system for measuring the scattered light whilethe cell is not rotating, and does not consider the cell width or theintegration time for a general-purpose automatic analyzer to measure thescattered light while the cell is rotating.

Patent Literature 5 limits the scattered light measuring direction to90°, and hence does not clarify whether to increase sensitivityaccording to various types of latex particle sizes.

Thus, the above disclosed techniques do not clarify a specificconfiguration capable of increasing sensitivity according to varioustypes of latex reagents and increasing sensitivity for scattered lightmeasurement while securing the integration time.

Solution to Problem

The present invention provides a configuration of arranging a pluralityof light receivers in a forward direction in a plane perpendicular tothe direction of cell rotation so as to increase sensitivity accordingto each of various types of latex particle sizes.

The automatic analyzer of the present invention includes a cell diskthat holds a cell containing a reaction mixture of a sample and areagent on a circumference thereof and repeats rotation and termination;and a scattered light measuring unit including a light source and alight receiver, that irradiates the cell with irradiation light from thelight source during rotation of the cell disk and measures the scatteredlight due to the reaction mixture in the cell. The scattered lightmeasuring unit includes a plurality of light receivers arranged in aplane perpendicular to the direction of cell movement due to therotation of the cell disk and receiving scattered light of each ofdifferent scattering angles. From the point of view of sufficientlysecuring the integration time at scattered light measurement, the anglebetween the optical axis of the irradiation light and the optical axisof scattered light received by each light receiver viewed from adirection perpendicular to a rotating plane of the cell disk ispreferably set to ±17.7° or less.

Preferably one of the plurality of light receivers is arranged at aposition for receiving scattered light with a scattering angle close tothe transmitted light axis, and the other one is arranged at a positionfor receiving scattered light between a first dark ring and a firstbright ring. For example, the first light receiver is arranged at aposition for receiving scattered light with a scattering angle of 30° orless, and the second light receiver is arranged at a position forreceiving the scattered light with at least part of the scatteringangles among the scattering angles of 30° to 50°.

Advantageous Effects of Invention

The automatic analyzer according to the present invention can receivescattered light at a plurality of angles while securing the integrationtime. Thus, the automatic analyzer can measure various types of latexreagents with high sensitivity. Thus, the automatic analyzer can achieveincreased sensitivity and precision for the conventional test items andcan be expected to handle new test items. Further, a diluted sample canbe used for detection, and hence the amount of samples can be reduced.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a graph illustrating an angular dependence of the scatteredlight intensity for a particle with a particle size of 0.1 μm and anangular dependence of the ratio of change when the particle size changesby 1%.

FIG. 2 is a graph illustrating an angular dependence of the scatteredlight intensity for a particle with a particle size of 0.2 μm and anangular dependence of the ratio of change when the particle size changesby 1%.

FIG. 3 is a graph illustrating an angular dependence of the scatteredlight intensity for a particle with a particle size of 0.3 μm and anangular dependence of the ratio of change when the particle size changesby 1%.

FIG. 4 is a graph illustrating an angular dependence of the scatteredlight intensity for a particle with a particle size of 0.4 μm and anangular dependence of the ratio of change when the particle size changesby 1%.

FIG. 5 is a graph illustrating an angular dependence of the scatteredlight intensity for a particle with a particle size of 0.6 μm and anangular dependence of the ratio of change when the particle size changesby 1%.

FIG. 6 is a graph illustrating an angular dependence of the scatteredlight intensity for a particle with a particle size of 0.7 μm and anangular dependence of the ratio of change when the particle size changesby 1%.

FIG. 7 is a graph illustrating an angular dependence of the scatteredlight intensity for a particle with a particle size of 0.8 μm and anangular dependence of the ratio of change when the particle size changesby 1%.

FIG. 8 is a graph illustrating an angular dependence of the scatteredlight intensity for a particle with a particle size of 0.9 μm and anangular dependence of the ratio of change when the particle size changesby 1%.

FIG. 9 is a graph illustrating an angular dependence of the scatteredlight intensity for a particle with a particle size of 1.0 μm and anangular dependence of the ratio of change when the particle size changesby 1%.

FIG. 10 is a graph illustrating an angular dependence of the scatteredlight intensity change ratio of a particle with a particle size of 0.1μm to 0.6 μm with respect to a particle size change of 1%.

FIG. 11 is a graph illustrating an angular dependence of the scatteredlight intensity for a particle with a particle size of 0.7 μm to 1.0 μmwith respect to the ratio of change in particle size by 1%.

FIG. 12 is an explanatory drawing of integration time estimation.

FIG. 13 is a schematic drawing of a scattered light measuring unitaccording to the present invention viewed from a direction perpendicularto a rotating plane of a cell disk.

FIG. 14 is a schematic drawing illustrating an entire configurationexample of an automatic analyzer according to the present invention.

FIG. 15 is an explanatory drawing of the transmitted light measuringunit.

FIG. 16 is a schematic drawing of the scattered light measuring unitaccording to the present invention.

FIG. 17 is a graph illustrating an experimental result of angulardependence of the ratio of change in the amount of scattered light dueto latex agglutination.

DESCRIPTION OF EMBODIMENTS

FIGS. 1 to 9 illustrate the results of calculation of an angulardependence of the scattered light intensity when one latex particle(particle size from 0.1 μm to 1.0 μm) in the water is irradiated withlight and an angular dependence of the ratio of change in the scatteredlight intensity when the particle size of a latex particle changes by 1%considering low concentration for high sensitivity measurement andassuming a case in which a small amount of constituent is contained inthe sample and only a few constituent agglutinates.

Here, the change ratio in the description is defined as a value afterchange divided by a value before change. Specifically, when there is nochange, the change ratio is calculated as 1. The light amount change (%)is defined as a value (a value after change−a value before change)divided by the value before change. Specifically, when there is nochange, the light amount change (%) is calculated as 0. These values areuseful as a simple approximation. The wavelength of irradiation light isset to 570 nm that has been used for conventional measurement oftransmitted light. When measured, the scattered light scattered in areaction mixture and transmitted through a glass window is measured inthe air, and hence these effects are approximated and considered in themeasurement. The above calculation is based on the discussion andcalculation in a wide range of the scattered light theories. One exampleof the scattered light theories is described by C. F. Bohren and D. R.Huffman: Absorption and Scattering of Light by Small Particles, J. Wiley& Sons, 1983.

FIG. 1 is a graph of a latex particle with a particle size of 0.1 μm;FIG. 2 is a graph of a latex particle with a particle size of 0.2 μm;FIG. 3 is a graph of a latex particle with a particle size of 0.3 μm;FIG. 4 is a graph of a latex particle with a particle size of 0.4 μm;FIG. 5 is a graph of a latex particle with a particle size of 0.6 μm;FIG. 6 is a graph of a latex particle with a particle size of 0.7 μm;FIG. 7 is a graph of a latex particle with a particle size of 0.8 μm;FIG. 8 is a graph of a latex particle with a particle size of 0.9 μm;and FIG. 9 is a graph of a latex particle with a particle size of 1.0μm.

As illustrated by the graph in FIG. 6, the scattered light intensity hasseveral peaks depending on the scattering angle. The range of scatteringangles from a scattering angle of 0° up to an angle of a first downwardconvex peak of the scattered light intensity is defined as a centralportion; an angle of a upward convex peak of the scattered lightintensity in the range in which the scattering angle is larger than thatof the central portion is defined as a bright ring; and an angle of adownward convex peak thereof is defined as a dark ring, which arenumbered sequentially from the central portion. More specifically, thenumber starts from the scattering angle of 0° followed by the centralportion, a first dark ring, a first bright ring, a second dark ring, asecond bright ring, and so on. These positions can be calculated fromthe wavelength of irradiation light, the size of a particle, therefractive index of the particle, and the refractive index of themedium. It is understood from FIG. 6 that the regions of a largescattering angle in the direction in which the change ratio of thescattered light intensity increases when the particle size changes by 1%are located in a central portion with an angle close to 0°, or betweenthe dark ring and the following bright ring such as between the firstdark ring and the first bright ring and between the second dark ring andthe second bright ring. The scattering light can be measured with highsensitivity by arranging a light receiver at each position in which thechange ratio increases for measurement.

Further, measurement can be made with high sensitivity by arranging thelight receiver at a position in which the change ratio decreases.Furthermore, measurement can also be made with high sensitivity in aregion of a scattering angle having a large amount of reduction in adirection in which the change ratio decreases such as by being locatedbetween the central portion and the dark ring or between the bright ringand the following dark ring such as before the first dark ring orbetween the first bright ring and the second dark ring. Thus, theaccuracy can be further increased by arranging a large number of lightreceivers in such a region and by measuring the increase or decrease inthe change ratio. Accordingly, it is useful to arrange a large number oflight receivers.

Next, FIG. 10 collectively illustrates the change ratios for particleswith a particle size of 0.1 μm to 0.6 μm; and FIG. 11 collectivelyillustrates the change ratios for particles with a particle size of 0.7μm to 1.0 μm. It is understood from FIG. 10 that for the particles witha particle size of 0.1 μm to 0.6 μm, the central portion with an anglenear 20°±10° is advantageous for increasing the sensitivity atmeasurement, considering that the region close to an angle of 0° is notsuitable for receiving scattered light because of incident irradiationlight. In contrast to this, it is understood from FIG. 11 that for theparticles with a particle size of 0.7 μm to 1.0 μm, the change ratiodecreases in the central portion with an angle of 20°±10°, and hence theregion with a scattering angle near 40°±10° in which a light receiver islocated between the first dark ring and the first bright ring isadvantageous for measuring the particles of such a particle size withhigh sensitivity. Thus, in order to handle the reagents of variousparticle sizes, scattered light detectors are desirably arranged in aplurality of positions in the central portion and between the first darkring and the first bright ring. More specifically, measurement can bemade with high sensitivity for any reagent of various reagent particlesizes by arranging an optical system such that the light receiving anglebecomes a plurality of angles equal to or less than 30° and equal to orgreater than 30°.

Next, referring to FIG. 12, the scattered light receiving angle and theintegration time will be described. FIG. 12 illustrates a cell viewedfrom above, namely, from the direction perpendicular to a rotating planeof a cell disk holding the cell and rotating (will be described laterreferring to FIG. 14). FIG. 12 is a schematic drawing illustrating thepositional relationship between transmitted light 16 b and scatteredlight 16 c from the central portion of the cell in which a reactionmixture 7 in the cell is irradiated with irradiation light 16 a from theleft hand side. For simplicity of explanation of integration timeestimation, the configuration is assumed such that each light beam widthis constant in the cell and the irradiation light is incidentperpendicularly to the cell wall surface. Note that the incidentirradiation light beam width lcw is made smaller than the cell width cwsince scattered light at a cell angle becomes stray light. Assuming thatcw is the cell width, lw is the total beam width to be considered, mw isthe left and right margins from the cell wall surface, and v is the cellrotation speed, an integration time t can be calculated from thefollowing expression (1).

t=(cw−2×mw−lw)/v  (1)

Assuming that lcw is the beam width of irradiation light irradiating thecell, ldw is the beam width of the scattered light, Cx is the opticalaxis of the irradiation light located at the cell wall surface, Dx isthe optical axis of the scattered light, and li is the distance betweenthe optical axis Cx and the optical axis Dx, lw can be calculated fromthe following expression (2).

lw=lcw/2+ldw/2+li  (2)

Further, using a cell optical path length L and an angle ψ between theoptical axis of the irradiation light and the optical axis for receivingthe scattered light viewed from above the cell, li can be calculatedfrom the following expression (3).

li=L/2×tan ψ  (3)

Considering the above, a maximum angle ψ₀ between the optical axis ofthe irradiation light and the optical axis for receiving the scatteredlight viewed from above the cell can be expressed by the followingexpression (4) using expressions (1), (2), and (3).

ψ₀=arctan((2cw−2vt−4mw−lcw−ldw)/L)  (4)

As long as the angle ψ between the optical axis of the irradiation lightand the optical axis for receiving the scattered light is equal to orless than ψ₀ satisfying the expression (4), light can be received at aplurality of angles against reduction in cell width.

In practice, an integration time of 2 msec or more, an irradiation lightbeam width lcw of 0.5 mm, and a scattered light beam width ldw of 0.5 mmneed to be secured depending on the amount of scattered light. Further,considering that the cell suffers from uneven formation and curvedsurface at corners, a left and right margin mw of about 0.5 mm isrequired. Furthermore, an optical path length L of 5 mm is substantiallystandard for transmitted light measurement. With a recent reduction incell width, the cell width cw is equal to or less than 2.5 mm and thecell rotation speed v is approximately 100 mm/sec or more. Thus, ψ₀ canbe approximated to 17.7° from the expression (4).

FIG. 13 illustrates a cell viewed from above indicating the relationshipbetween the transmitted light 16 b and the scattered light 16 c viewedfrom the direction perpendicular to a rotating plane of the cell disk.From above, when scattered light at a plurality of scattering angles isobtained, each scattered light receiver is arranged such that the anglebetween the transmitted light 16 b and the scattered light 16 c viewedfrom above is equal to or less than ±ψ₀. Thereby, the scattered light ata plurality of angles can be easily obtained while securing theintegration time. Note that a plurality of scattered light receivers arerespectively configured to receive light transmitted through the samewall surface as the cell wall surface through which the transmittedlight passes. In order to improve the sensitivity at scattered lightmeasurement, it is essential to reduce the receiving of scattered lightoccurring on the cell wall surface as much as possible. Accordingly, thecell wall surface needs to be optically flat with less surfaceasperities. However, the cells are manufactured by injection molding andhence an increase in optically flat surfaces leads to an increase inmanufacturing costs. The surface through which the transmitted lightpasses has already been made an optically flat surface for measuring theamount of transmitted light. In light of this, the scattered lightpassing through the same wall surface as that through which thetransmitted light passes can be measured without increasing the costsfor cell formation.

Note that it is understood from FIGS. 10 and 11 that an appropriatereagent particle size differs depending on the angle for measuring thescattered light. For example, in the case of a measurement system forreceiving the scattered light in the direction of an angle of 40°,measurement can be made with high sensitivity by setting the reagentparticle size to 0.8 to 1.0 μm; and in the case of a measurement systemfor receiving the scattered light in the direction of an angle of 20°,measurement can be made with high sensitivity by setting the reagentparticle size to 0.6 μm or less.

Next, an example of the automatic analyzer according to the presentinvention will be described. FIG. 14 is a schematic drawing illustratingan entire configuration example of the automatic analyzer according tothe present invention. This automatic analyzer includes a scatteredlight measuring unit for increasing sensitivity. The automatic analyzermainly includes three types of disks: a sample disk 3, a reagent disk 6,and a cell disk 9, a pipetting mechanism for moving a sample and areagent between the disks, a control unit for controlling the disks, ameasuring unit, an analysis unit for processing the measured data, adata storage unit for storing the control data, the measured data, andthe analyzed data, an input unit and an output unit for inputting andoutputting data from and to the data storage unit.

The sample disk 3 has a plurality of sample cups 2 holding a sample 1 ona circumference thereof. The reagent disk 6 has a plurality of reagentbottles 5 holding a reagent 4. The cell disk 9 has a plurality of cells8 on a circumference thereof. Each cell 8 holds a reaction mixture 7made by mixing the sample 1 and the reagent 4 thereinside. The samplepipetting mechanism 10 moves a constant amount of sample 1 from thesample cup 2 to the cell 8. The reagent pipetting mechanism 11 moves aconstant amount of reagent 4 from the reagent bottle 5 to the cell 8.The stirring unit 12 stirs and mixes the sample 1 and the reagent 4 inthe cell 8. When the analysis is completed, the cleaning unit 14discharges the reaction mixture 7 from the cell 8 and cleans the cell 8.The cleaned cell 8 receives another sample 1 from the sample pipettingmechanism 10 again and a new reagent 4 is received from the reagentpipetting mechanism 11 to be used for another reaction. The cell 8 isimmersed in a constant-temperature fluid 17 in a constant-temperaturebath in which the temperature and the flow rate are controlled. The cell8 is moved in a state in which the cell 8 and the reaction mixture 7therein are maintained at a constant temperature. Water is used as theconstant-temperature fluid 17. The constant-temperature fluid controlunit controls the temperature and the flow rate to maintain theconstant-temperature fluid. The temperature is adjusted to 37±0.1° C. asthe reaction temperature. The transmitted light measuring unit 13 andthe scattered light measuring unit 31 are installed on a part of thecircumference of the cell disk.

As illustrated in FIG. 15, the transmitted light measuring unit 13irradiates the cell 8 with light from a halogen lamp light source 15 a.The transmitted light beam 16 a is divided by a diffraction grating 22and received by a photodiode array 21 having photodiodes arranged in anarray. The wavelength of the received light are 340 nm, 405 nm, 450 nm,480 nm, 505 nm, 546 nm, 570 nm, 600 nm, 660 nm, 700 nm, 750 nm, and 800nm.

As illustrated in FIG. 16, the scattered light measuring unit 31irradiated the cell 8 with irradiation light 16 a from an LED lightsource 15 b. The transmitted light 16 b was received by a transmittedlight receiver 32 as the monitor. The scattered light beams 16 c weremeasured by scattered light receivers 33 a and 33 b. The scattered lightreceivers 33 a and 33 b were arranged at scattered light receivingangles θ1 and θ2, which are 20° and 40° respectively. As the LED lightsource 15 b, L660-02V with an irradiation light wavelength of 660 nmmanufactured by Epitex Incorporation was used. According to the presentconfiguration, the scattered light receivers were arranged at angles of20° and 40°, but optical systems such as a fiber and lens may bearranged in the same place so as to guide light to the scattered lightreceivers arranged in other places. Further, the scattered lightreceivers 33 a and 33 b were arranged in positions for receivingscattered light scattered downward relative to the irradiation light 16a, but may be arranged in positions for receiving scattered lightscattered at an angle θ3 upward relative to the irradiation light 16 asuch as the scattered light receiver 33 c.

The angles of the optical axis of the scattered light was adjusted bymonitoring the amount of light of the scattered light receiver 33 a onthe downward side and the scattered light receiver 33 c on the upwardside. More specifically, another scatterer was arranged at the positionof the reaction mixture 7 and the scattered light receiver 33 c wasadjusted at an angle of 20° on the upward side by matching the amount oflight between the scattered light receiver 33 a and the scattered lightreceiver 33 c. This facilitates the angle adjustment. When the scatteredlight receivers 33 a, 33 b, and 33 c and the transmitted light receiver32 are configured to have the same angle as the angle θ1 on the downwardside and the angle θ3 on the upward side as a single integrated unit,the positional adjustment of the transmitted light receiver 32 and likeand the positional adjustment of the entire unit can be made by matchingthe amount of light between the scattered light receiver 33 a and thescattered light receiver 33 c, which is more advantageous for reducingthe adjustment time than the individual positional adjustment of eachlight receiver. If only the angle of 20° on the upward side is used,noise due to the positional change in the light source is measured, butthe positional change in the light source can be cancelled by measuringthe two positions at the angle of 20° on the upward side and on thedownward side, thereby increasing sensitivity.

An LED was used as the light source 15 b, but a laser, a xenon lamp, ora halogen lamp may be used. The cell had a cell width of 2.5 mm and anoptical path length of 5 mm, the beam width was 0.5 mm for both theirradiation light and the scattered light, and the cell rotation speedwas 200 mm/sec to secure an integration time of 5 msec.

The angle ψ between the optical axis of the irradiation light and theoptical axis for receiving the scattered light viewed from above thecell was equal to or less than 17.7° considering an error in mountingprecision. Thereby, light can be received at a plurality of scatteringangles while securing at least 2 msec or more as the integration time.The present example secured 5 msec. Even if the cell size decreasesextremely, any latex reagent of various particle sizes can be handledand a sufficient integration time can be secured by arranging ascattered light receiver on a plane perpendicular to the direction ofcell rotation, namely, by arranging a scattered light receiver in aplane perpendicular to the direction of cell movement by cell diskrotation.

The analysis of the amount of constituent in the sample 1 is performedin the following procedure. First, the sample pipetting mechanism 10dispenses a constant amount of sample 1 in the sample cup 2 into thecell 8. Next, the reagent pipetting mechanism 11 dispenses a constantamount of reagent 4 in the reagent bottle 5 into the cell 8. Whendispensed, the sample disk 3, the reagent disk 6, and the cell disk 9are rotatably driven by the respective drive units under the control ofthe control unit to move the sample cup 2, the reagent bottle 5, and thecell 8 with the timing of the pipetting mechanism. Then, the stirringunit 12 stirs the sample 1 and the reagent 4 in the cell 8 to make thereaction mixture 7. Note that FIG. 14 is a simplified drawingillustrating only one reagent disk and reagent pipetting mechanism, buttypically two reagent disks, reagent pipetting mechanisms, and stirringunits are used.

Each time the light passes through the measurement positions of thetransmitted light measuring unit 13 and the scattered light measuringunit 31 while the cell disk 9 is rotating, the transmitted light and thescattered light of the reaction mixture 7 are measured and sequentiallyaccumulated as reaction process data in the data storage unit throughthe measuring unit. After the optical measurement for about 10 minutes,the cleaning mechanism 14 cleans the inside of the cell 8 and then theprocess moves on to the next analysis. During the period, if necessary,the reagent pipetting mechanism 11 adds another reagent 4 to the cell 8for pipetting, and the stirring unit 12 stirs the reagent 4 to befurther measured for a specific time. Thus, the reaction process data ofthe reaction mixture 7 is stored in the data storage unit at a specifictime interval. The analysis unit analyzes the accumulated reactionprocess data to determine the amount of constituent based on thecalibration curve data for each test item. The data required for eachunit to control and analyze is inputted from the input unit to the datastorage unit. The calibration curve data is maintained in the datastorage unit. The output unit outputs various data, results, and alarmsthrough a display or the like.

FIG. 17 illustrates the experimental results of the angular dependenceof the ratio of change in scattered light for the latex agglutinationreaction according to the present example. The CRP reagent (Nanopia CRPmanufactured by Sekisui Chemical Co., Ltd.) was used as the reagent, andthe CRP Calibrator (manufactured by Sekisui Chemical Co., Ltd.) wasdiluted and used as the sample. The light amount change (%) in theamount of transmitted light in the direction of an angle of 0° with aconcentration of 0.01 mg/dL was 0.13%, and the light amount change (%)in the direction of an angle of 20° was 0.71%, which means that five ormore times the light amount change (%) was detected and it was confirmedthat the detection was made with increased sensitivity.

REFERENCE SIGNS LIST

-   1 sample-   2 sample cup-   3 sample disk-   4 reagent-   5 reagent bottle-   6 reagent disk-   7 reaction mixture-   8 cell-   9 cell disk-   10 sample pipetting mechanism-   11 reagent pipetting mechanism-   12 stirring unit-   13 transmitted light measuring unit-   14 cleaning unit-   15 light source-   15 a halogen lamp-   15 b LED-   16 light-   16 a irradiation light-   16 b transmitted light-   16 c scattered light-   17 constant-temperature fluid-   21 photodiode array-   22 diffraction grating-   31 scattered light measuring unit-   32 transmitted light receiver-   33 a, 33 b, 33 c scattered light receiver

What is claimed is:
 1. An automatic analyzer comprising: a cell discthat holds a cell containing a reaction mixture in which a sample andreagent are mixed with each other on a circumference thereof and repeatsrotation and termination; a light source; a plurality of optical systemsconfigured to receive scattered light at different angles, the scatteredlight being generated upon irradiation of the reaction mixture in thecell with irradiation light from the light source; and a scattered lightreceiver configured to receive light guided by the plurality of opticalsystems, wherein the plurality of optical systems are arranged in aplane perpendicular to a rotation direction of the cell disc.
 2. Theautomatic analyzer according to claim 1, wherein the plurality ofoptical systems include fibers or lenses.